Effect of intravenous ghrelin administration, combined with alcohol, on circulating metabolome in heavy drinking individuals with alcohol use disorder

Abstract

Background: Ghrelin may influence several alcohol-related behaviors in animals and humans by modulating central and/or peripheral biological pathways. The aim of this exploratory analysis was to investigate associations between ghrelin administration and the human circulating metabolome during alcohol exposure in nontreatment seeking, heavy drinking individuals with alcohol use disorder (AUD). Methods:We used serum samples from a randomized, crossover, double-blind, placebo-controlled human laboratory study with intravenous (IV) ghrelin or placebo infusion in two experiments. During each session, participants received a loading dose (3 µg/kg) followed by continuous infusion (16.9 ng/kg/min) of acyl ghrelin or placebo.The first experiment included an IV alcohol self-administration (IV-ASA) session and the second experiment included an IV alcohol clamp (IV-AC) session, both with the counterbalanced infusion of ghrelin or placebo. Serum metabolite profiles were analyzed from repeated blood samples collected during each session. Results:In both experiments, ghrelin infusion was associated with an altered serum metabolite profile, including significantly increased levels of cortisol (IV-ASA qvalue = 0.0003 and IV-AC q < 0.0001), corticosterone (IV-ASA q = 0.0202 and IV-AC q < 0.0001), and glycochenodeoxycholic acid (IV-ASA q = 0.0375 and IV-AC

Alcohol use associated alterations in the circulating metabolite profile in the general population and in individuals with major depressive disorder

“…Heavy alcohol use has been associated with an altered metabolome (for a review see Voutilainen and Kärkkäinen, 2019). For example, increased levels of glutamate, citrate, alanine, phenylalanine, tyrosine, glucose, docosahexaenoate, 2piperidone and phosphatidylcholine diacyls, and decreased levels of glutamine, serotonin, asparagine, hydroxysphingomyelins, gamma-aminobutyric acid (GABA) and phosphatidylcholine acyl-alkyls have been associated with heavy alcohol use (Heikkinen et al, 2019;Jaremek et al, 2013;Kärkkäinen, Farokhnia, et al, 2021;Kärkkäinen, Kokla, et al, 2021;Lehikoinen et al, 2018;Würtz et al, 2016). In a prospective study with an over 30 5 years' follow-up, changes in the circulating metabolome, e.g., decreased levels of serotonin and asparagine, preceded the diagnosis of diseases related to alcohol use (Kärkkäinen et al, 2020).…”